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We could make good cartilage from i PSCs and transplant that purified cartilage to that small lesion.
The breakthrough sidestepped the embryo controversy, offering researchers an unlimited supply of stem cells. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for reprogramming mature cells into what are now called induced pluripotent stem cells, or i PS cells.
Still, the march toward new treatments has been halting. Yamanaka directs Kyoto University’s Center for i PS Cell Research and Application. Masayo Takahashi and her colleagues at the Riken Center for Developmental Biology had great success using i PS cells to treat macular degeneration.
He also leads a small research lab at the Gladstone Institutes, affiliated with the University of California, San Francisco, where his group studies the molecular mechanisms that underlie pluripotency and the factors that induce reprogramming. Our conversation has been edited for length and clarity. There has been great enthusiasm and confidence for nearly 20 years that the use of stem cells will lead to powerful new treatments for a range of diseases. They took skin cells from a 70-year-old patient and derived i PS cells from them. Before the transplantation for the second patient, we checked the genome sequence of the patient’s i PS cells and we identified a mutation in the cells. The pluripotent stem cells [have the] ability to proliferate rapidly and infinitely. After multiple cell cycles, the chances of mutations increases. We are developing allogenic stem cell lines — stem cells from donors.
Now, 10 years after your discovery, what treatments have been developed? They then differentiated the stem cells (directed them “back down” the normal developmental path) to become adult retinal cells. This could include mutation to produce an oncogene that can cause cancer. They would not be the patient’s own, but compatible cells to transplant into the patient, much like blood transfusions with compatible blood types.
That’s very different from the way stem cell treatments were originally described to the public.
It was going to be “personalized” medicine — using the patient’s own stem cells to generate the adult cells without risk of rejection. But the diseases I described are caused by loss of function of just one type of cell.But soon after, we realized we are making new ethical issues. What is needed before patients can receive stem cell treatments for the 10 or so diseases you identified? We can make a human kidney or human pancreas in pigs if human i PS cells are injected into the embryo. Well, we realized that it would take a great deal of time and would be unrealistically expensive to carry out the deep sequencing and animal studies for each patient’s cells. We can help just a small portion of patients by stem cell therapy. Parkinson’s disease is caused by failure of very specialized brain cells that produce dopamine.How many compatible donor cell lines do you expect will be needed to cover the Japanese population? One particular line — just one — can work for 17 percent of the Japanese population. For example, target diseases for cell therapy are limited. Heart failure is caused by loss of function of cardiac heart cell. We can make that one type of cell from stem cells in a large amount, and by transplanting those cells, we should be able to rescue the patient.Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, re-energized the field by devising a technique to “reprogram” any adult cell, such as a skin cell, and coax it back to its earliest “pluripotent” stage.From there it can become any type of cell, from a heart muscle cell to a neuron.These were transplanted into the patient’s eye to treat the disease. We are performing rigorous quality tests, including sequencing the stem cells’ genomes to be sure the cells are free from cancer-causing mutations.We perform tests on adult retinal cells generated from these stem cells to assure that they function as normal retinal cells, and those cells are transplanted into mice or rats for a year to assure they are safe.We estimate that altogether about 100 lines will suffice for the 100 million people in Japan. There are about 10: Parkinson’s, retinal and corneal diseases, heart and liver failure, diabetes and only a few more — spinal cord injury, joint disorders and some blood disorders. But many other diseases are caused by multiple types of cell failures, and we cannot treat them with stem cell therapy.How many lines would be needed for the more diverse United States population? What are the prospects for the other nine or so diseases that you say stem cell treatments can address?